Effects of Hyperthermia Combined Platinum-based Drugs on Ovarian Cancer Cell Lines SKOV3

Objective To investigate the effects and mechanisms of hyperthermia combined with various platinum-based drugs cis-platinum (DDP), carboplatin (CBP), oxaliplatin (OXA) on the proliferation and apoptosis of ovarian cancer cell lines SKOV3. Methods SKOV3 cells were treated with different concentrations of anticancer drugs DDP (final concentration respectively 0, 1.25, 2.5, 5.0, 10.0, 20.0 μg/mL), CBP and OXA (both final concentration respectively 0, 2.5, 5.0, 10.0, 20.0, 40 μg/mL) at a temperature of 42 ℃ for hyperthermia or 37 ℃ for normal temperature. Methyl thiazolyl tetrazolium (MTT) method was used to test growth ratios of ovarian cancer cell lines SKOV3. Real-time PCR was adopted to detect the expression level of excision repair cross-complementing group 1 (ERCC1) and Survivin mRNA in SKOV3 cells. Results DDP, CBP and OXA inhibited the growth of SKOV3 in a dose-dependent manner （P<0.05). Hyperthermia could increase the sensitivity of SKOV3 to cis-platinum，carboplatin and oxaliplatin （P<0.05). The half inhibitory concentration (IC₅₀） values of DDP, CBP and OXA were （7.271±0.096） μg/mL, （37.609±0.779） μg/mL and （28.328±0.698） μg/mL respectively. When combined with hyperthermia, the IC₅₀ values of DDP, CBP, and OXA were （2.075±0.244） μg/mL, （19.591±0.453） μg/mL, （19.089±0.424） μg/mL （P<0.05). The increased sensitivity index was 2.075±0.244 for cis-platinum, 1.92±0.044 for carboplatin, 1.484±0.039 for oxaliplatin. After the treatment of hyperthermia, the expression of ERCC1 and Survivin mRNA showed downward trend. ERCC1 decreased more significantly in the group of hyperthermia combined with carboplatin, and Survivin decreased more significantly in the group of hyperthermia combined with oxaliplatin (P<0.05). Conclusion Hyperthermia can enhance the sensitivity of ovarian cancer SKOV3 cells to platinum-based drugs, which may be related to the down regulation of ERCC1 and Survivin expression.